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The ‘short’ and ‘long-term’ benefits of pharmacological interventions to treat orthostatic hypotension (OH) remain unclear. The aim was to systematically examine the published literature on the effectiveness of different drug regimens for the treatment of OH.Systematic review.MEDLINE (1950-Week 7, 2011), EMBASE (1980-Week 7, 2011), CINAHL (1981-Week 7, 2011) databases and hand-searching of bibliographies were used to identify suitable papers.Studies selected were those, which investigated drug treatment of OH in a single- or double-blind randomised controlled trial (RCT) in humans over 18 years of age.Data were extracted from suitable full-text articles by three investigators independently.The 13 trials met the criteria for systematic review amongst which was considerable variation in the size of postural blood pressure (BP) change with active treatment. However, there was evidence that commonly used drugs midodrine or fludrocortisone therapy did increase standing or head-up-tilt (HUT) systolic blood pressure in certain patient groups.The evidence that pharmacological therapy is of benefit for the treatment of OH is limited by the lack of good quality clinical trial evidence. Further well-designed RCTs of pharmacological treatment of OH investigating the impact on postural symptoms as well as actual BP changes are needed.